The chemokine receptor CXCR4 has been identified as a co-receptor for the infection of cells by HIV and is thought to play a key role in the progression to AIDS. We have used a highly diverse, oriented peptide library approach to identify small peptide ligands for CXCR4. The goals of this research are to characterize the CXCR4 inhibitors identified so far, identify additional lead series, and carry out the optimization of the lead series with respect to antiviral potency and selectivity. The properties of the consensus-identified CXCR4-binding peptides will be characterized according to their signalling properties, their ability to inhibit gp120 binding, their cellular toxicity, their specificity for the CXCR4 receptor, and their ability to block HIV infection. The identification and clinical development of a peptide which blocks the binding of HIV to CXCR4 will result in an important new therapeutic class in the arsenal for use against AIDS. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE